Pestell was appointed an Officer of the Order of Australia for distinguished service to medicine and medical education in 2019 by Queen Elizabeth II.

Pestell led the effort for renewal of the National Cancer Institute designation, and supported Dr. Mandelblatt in founding the Capital Breast Care Center with Andrea Jung of the Avon Foundation.

[10] From 2005 to 2015, Pestell was Director of the Sidney Kimmel Cancer Center in Philadelphia, Pennsylvania, and Executive Vice President of Thomas Jefferson University.

In January 2019, Pestell was named Vice Chairman of the Board of the CytoDyn, Inc., which acquired his prior company, ProstaGene, in November 2018.

[16][17] As the Chief Medical Officer, he established the company's cancer clinical trial for the use of a CCR5 inhibitor (leronlimab)[18] and FDA fast track designation in May 2019.

[19] He exited CytoDyn in July 2019 and is currently member of the Wistar Institute Cancer Center Philadelphia and Blumberg Distinguished Professor.

[24] Pestell showed that nuclear receptors (estrogen, androgen and PPARγ) are acetylated, and that this event is rate-limiting in hormone signaling and growth control- thus identifying a new target for cancer therapy.

His laboratory demonstrated this was a general mechanism conserved among nuclear receptors that affect diverse biological processes.

[25] In the cell cycle field, Pestell's research has shown the discovery that cyclins are direct transcriptional targets of oncogenic and tumour suppressor signals.

[35] Pestell is the founder of four biotechnology companies and holds patents in the areas of cancer diagnostics, therapeutics and technologies.